Candida albicans is among the major human fungal pathogens, causing both mucosal and deep tissue infections. A significant risk factor for invasive C. albicans infection is the presence of an implanted medical device, which provides a surface for biofilm formation. The biofilm creates a protected microenvironment for survival of the pathogen. The immediate goal of studies here proposed is to define the key C. albicans genes and regulatory pathways that govern biofilm formation, and to move forward to yield mechanistic insight. The proposed studies build upon progress in the last funding period that defined two biofilm transcriptional regulators, Bcr1 and Zap1/Csr1, along with several of their functional target genes. Our main objectives now are (1) to define the interactions among Bcr1 regulated gene products that promote biofilm adherence, (2) to determine roles of Zap1 target gene families in accumulation of extracellular matrix material, and (3) to define the functions of newly discovered transcriptional regulators that promote adherence of yeast-form cells PUBLIC HEALTH RELEVANCE: Presence of an implanted medical device, such as a venous catheter, is a major risk factor for lethal disseminated Candida infections. Proposed studies will improve our understanding of mechanisms that permit Candida growth on implanted devices. The mechanistic understanding will permit longer-term development of new therapeutic and diagnostic strategies.